Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention

Cancer recurrence and metastasis, following successful treatment, constitutes a critical threat in clinical oncology and are the leading causes of death amongst cancer patients. This phenomenon is largely attributed to metastatic tumor dormancy, a rate-limiting stage during cancer progression, in which disseminated cancer cells remain in a viable, yet not proliferating state for a prolonged period. Dormant cancer cells are characterized by their entry into cell cycle arrest and survival in a quiescence state to adapt to their new microenvironment through the acquisition of mutations and epigenetic modifications, rendering them resistant to anti-cancer treatment and immune surveillance. Under favorable conditions, disseminated dormant tumor cells ‘re-awake’, resume their proliferation and thus colonize distant sites. Due to their rarity, detection of dormant cells using current diagnostic tools is challenging and, thus, therapeutic targets are hard to be identified. Therefore, unraveling the underlying mechanisms required for keeping disseminating tumor cells dormant, along with signals that stimulate their “re-awakening” are crucial for the discovery of novel pharmacological treatments. In this review, we shed light into the main mechanisms that control dormancy induction and escape as well as emerging therapeutic strategies for the eradication of metastatic dormant cells, including dormancy maintenance, direct targeting of dormant cells and re-awakening dormant cells. Studies on the ability of the metastatic cancer cells to cease proliferation and survive in a quiescent state before re-initiating proliferation and colonization years after successful treatment, will pave the way toward developing innovative therapeutic strategies against dormancy-mediated metastatic outgrowth.     

Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis

Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 expression in the epidermis. Fibronectin (FN)—known to influence inflammation and keratinocyte hyperproliferation via α5β1 integrin in psoriasis—was also decreased. Syndecan-1 and -4 expression was analyzed in freshly isolated lesional psoriatic human keratinocytes (PHK) characterized based on their proliferation and differentiation properties. mRNA levels of syndecan-1 were similar between healthy and PHK, while syndecan-4 was significantly decreased. Cell growth and release of the pro-inflammatory Tumor Necrosis Factor-alpha (TNFα) were selectively and significantly induced in PHKs plated on FN. Results from co-culture of healthy keratinocytes and psoriatic fibroblasts led to the speculation that at least one factor released by fibroblasts down-regulate syndecan-1 expression in PHK plated on FN. To assay if biological treatments for psoriasis target keratinocyte proliferation, gelatin-based patches enriched with inteleukin (IL)-17α or TNFα blockers were prepared and tested using a full-thickness healthy epidermal model (Phenion^®). Immunohistochemistry analysis showed that both blockers impacted the localisation of syndecan-1 within the refined epidermis. These results provide evidence that syndecans expression are modified in psoriasis, suggesting that they may represent markers of interest in this pathology.     

Volatile fraction of commercial thyme honeys produced in Mediterranean regions and key volatile compounds for geographical discrimination: A chemometric approach

The aim of the present study was to investigate the volatile fraction and discriminate 34 commercial thyme honeys from Morocco, Egypt, Spain, and Greece according to geographical origin, using key volatile compounds in combination with chemometrics. Sixty-two volatile compounds belonging to different classes were identified and semi-quantified using headspace solid phase micro-extraction coupled to gas chromatography/mass spectrometry (HS-SPME-GC/MS). Applying chemometric analyses to 17 volatiles (p < 0.05), honeys were successfully discriminated according to geographical origin. Correct classification rate was 88.2% using the cross-validation method. Volatile compounds proved to be a powerful tool for discriminating commercial thyme honeys from different countries.     

Effect of moisture on salmonella spp. heat resistance in cocoa and hazelnut shells

The heat resistance of food-poisoning outbreak and non-outbreak associated strains of Salmonella (S. Enteritidis, S. Montevideo, S. Napoli, S. Oranienburg, S. Poona, S. Senftenberg and S. Typhimurium) was established in confectionery-related materials such as crushed cocoa bean and hazelnut shells at low moisture contents (≤ 4% w/w). The two most heat resistant strains in cocoa and hazelnut shells at ca. 4% w/w moisture were S. Oranienburg and S. Enteritidis PT30. Both strains were associated with outbreaks from dried materials. Their D_100°C values were ca. 2.5 min in crushed cocoa bean shells and 7–11 min in crushed hazelnut shells. Addition of moisture to ca. 7% w/w markedly reduced D-values (D_80°C of 2–4.5 min) for both strains in the two matrices.     

Molecular Advances in Preeclampsia and HELLP Syndrome

Preeclampsia (PE) constitutes one of the principal reasons for maternal and perinatal morbidity and mortality worldwide. The circumstance typically implicates formerly healthful normotensive women, after 20 weeks of gestation, typically withinside the third trimester, without regarded threat elements or past deliveries. PE can be further complicated with hemolysis and thrombocytopenia, leading to the emergence of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low platelets). Both conditions are classified as hypertensive diseases of pregnancy (HDP), and their pathogenesis has been linked to an excessive maternal inflammatory response, accompanied by enhanced endothelial activation. Several studies have found that in pregnancies affected by PE/HELLP, von Willebrand factor (vWF) antigen levels (vWF:Ag) are significantly elevated, while its cleaving protease (ADAMTS-13, A Disintegrin-like and Metalloprotease with Thrombospondin type 1 motif, member 13) activity is normal to decreased. Furthermore, the higher urine excretion of the terminal complement complex C5b-9, as well as its greater deposition in the placental surface in preeclamptic women, imply that the utero-placental unit’s distinctive deficits are intimately tied to disproportionate complement activation. The goal of this updated evaluation is to provide the most up-to-date molecular advances in the pathophysiology of PE/HELLP syndromes. Recent medical data on vWF:Ag levels in patients with PE, ADAMTS-13, and dysregulation of the complement system, are highlighted and evaluated. Furthermore, we discuss the relationship between those entities and the progression of the disease, as well as their significance in the diagnostic process. Finally, considering the difficulties in analyzing and controlling those symptoms in pregnant women, we can provide a current diagnostic and therapeutic algorithm.     

Prospective environmental life cycle assessment of nanosilver T-shirts

A cradle-to-grave life cycle assessment (LCA) is performed to compare nanosilver T-shirts with conventional T-shirts with and without biocidal treatment. For nanosilver production and textile incorporation, we investigate two processes: flame spray pyrolysis (FSP) and plasma polymerization with silver co-sputtering (PlaSpu). Prospective environmental impacts due to increased nanosilver T-shirt commercialization are estimated with six scenarios. Results show significant differences in environmental burdens between nanoparticle production technologies: The "cradle-to-gate" climate footprint of the production of a nanosilver T-shirt is 2.70 kg of CO(2)-equiv (FSP) and 7.67-166 kg of CO(2)-equiv (PlaSpu, varying maturity stages). Production of conventional T-shirts with and without the biocide triclosan has emissions of 2.55 kg of CO(2)-equiv (contribution from triclosan insignificant). Consumer behavior considerably affects the environmental impacts during the use phase. Lower washing frequencies can compensate for the increased climate footprint of FSP nanosilver T-shirt production. The toxic releases from washing and disposal in the life cycle of T-shirts appear to be of minor relevance. By contrast, the production phase may be rather significant due to toxic silver emissions at the mining site if high silver quantities are required.     

Does the presence of desert dust modify the effect of PM10 on mortality in Athens, Greece?

Recent reports investigate whether windblown desert dust may exacerbate the short-term health effects associated with particulate pollution in urban centers. We have tested this hypothesis by using daily air pollution and mortality data for Athens, Greece during the period 2001-2006.We investigated the effects of exposure to particulate matter with aerodynamic diameter < 0 μg/m³ (PM₁₀) on total and cause specific mortality, during days with and without windblown desert dust, for all ages, stratified by age groups and by sex. We identified 141 dust days between 2001 and 2006. We used Poisson regression models with penalized splines to control for possible confounding by season, meteorology, day of the week and holiday effect.A 10 μg/m³ increase in PM₁₀ was associated with a 0.71% (95% confidence interval (CI): 0.42% to 0.99%) increase in all deaths. The effects for total and cause specific mortality were greater for those ≥ 75 years of age, while for total mortality higher effects were observed among females. The main effect of desert dust days and its interaction with PM₁₀ concentrations were significant in all cases except for respiratory mortality and cardiovascular mortality among those < 75 years. The negative interaction pointed towards lower particle effects on mortality during dust events.We found evidence of modification of the adverse health effects of PM₁₀ on mortality in Athens, Greece with desert dust events: the particle effects were significantly higher during non-desert dust days. Our analyses indicate that traffic related particles, which prevail on non-desert dust days, have more toxic effects than the ones originating from long-range transport, such as Sahara dust.